Correlation between 6q25.3 deletion status and survival in pediatric intracranial ependymomas.
ABSTRACT Losses and rearrangements of genetic material on chromosome 6q are frequently found in several human malignancies, including primary central nervous system tumors. We previously used microsatellite analysis of ependymomas to identify frequent deletions in regions 6q15 approximately q16, 6q21 approximately q22.1, and 6q24.3 approximately q25.3. To refine our preliminary analysis of potential prognostic regions, we used a panel of 25 microsatellite markers located between 6q15 and 6qter in 49 pairs of matched normal and tumor specimens from 28 children and 21 adults with ependymoma. Allelic deletions were detected in 34 of 49 patients (69%), and two common regions of deletions (6q24.3 and 6q25.2 approximately q25.3) were identified. A short segment of approximately 0.4 Mb between D6S1612 and D6S363 on 6q25.3, containing the SNX9 and SYNJ2 genes, exhibited the highest number of aberrations (n = 38). Pediatric tumors showed slightly fewer aberrations (64%) than adult tumors (76%) and also predominantly exhibited small interstitial deletions, in contrast to the extensive losses of genetic material in adults. Pediatric anaplastic intracranial (supra- and infratentorial) ependymomas harboring the 6q25.3 deletion (n = 9) showed significantly longer overall survival than did patients of the same group without the aberration (n = 6), independent of the extent of resection (P = 0.013). This supports the identified deletion on 6q25.3 as a candidate favorable prognostic parameter and warrants further investigation.
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ABSTRACT: We have examined expression of microRNAs (miRNAs) in ependymomas to identify molecular markers of value for clinical management. miRNAs are non-coding RNAs that can block mRNA translation and affect mRNA stability. Changes in the expression of miRNAs have been correlated with many human cancers. We have utilized TaqMan Low Density Arrays to evaluate the expression of 365 miRNAs in ependymomas and normal brain tissue. We first demonstrated the similarity of expression profiles of paired frozen tissue (FT) and paraffin-embedded specimens (FFPE). We compared the miRNA expression profiles of 34 FFPE ependymoma samples with 8 microdissected normal brain tissue specimens enriched for ependymal cells. miRNA expression profiles were then correlated with tumor location, histology and other clinicopathological features. We have identified miRNAs that are over-expressed in ependymomas, such as miR-135a and miR-17-5p, and down-regulated, such as miR-383 and miR-485-5p. We have also uncovered associations between expression of specific miRNAs which portend a worse prognosis. For example, we have identified a cluster of miRNAs on human chromosome 14q32 that is associated with time to relapse. We also found that miR-203 is an independent marker for relapse compared to the parameters that are currently used. Additionally, we have identified three miRNAs (let-7d, miR-596 and miR-367) that strongly correlate to overall survival. We have identified miRNAs that are differentially expressed in ependymomas compared with normal ependymal tissue. We have also uncovered significant associations of miRNAs with clinical behavior. This is the first report of clinically relevant miRNAs in ependymomas.PLoS ONE 01/2011; 6(10):e25114. · 4.09 Impact Factor